A COPD medication delivery device option: an overview of the NEOHALER

Indication and Boxed Warning INDICATION ARCAPTA NEOHALER (indacaterol) is a long-acting beta 2 -adrenergic agonist (LABA), SEEBRI NEOHALER (glycopyrrolate) is an anticholinergic, and UTIBRON NEOHALER (indacaterol and glycopyrrolate) is a combination of indacaterol and glycopyrrolate; all are indicated for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Important limitations: ARCAPTA NEOHALER and UTIBRON NEOHALER are not indicated to treat acute deteriorations of COPD and are not indicated to treat asthma. IMPORTANT SAFETY INFORMATION WARNING: ASTHMA-RELATED DEATH Long-acting beta 2 -adrenergic agonists (LABAs) increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of all LABAs, including indacaterol, the active ingredient in ARCAPTA NEOHALER, and one of the active ingredients in UTIBRON NEOHALER. The safety and efficacy of ARCAPTA NEOHALER or of UTIBRON NEOHALER in patients with asthma have not been established. ARCAPTA NEOHALER and UTIBRON NEOHALER are not indicated for the treatment of asthma. Please see additional Important Safety Information for ARCAPTA NEOHALER, SEEBRI NEOHALER, and UTIBRON NEOHALER on slides 10-13 of this presentation and accompanying full prescribing information, including BOXED WARNINGS. References: 1. UTIBRON NEOHALER [prescribing information]. 2. SEEBRI NEOHALER [prescribing information]. 3. ARCAPTA NEOHALER [prescribing information]. 2

Choosing an appropriate inhalation device is important in the treatment of chronic obstructive pulmonary disease (COPD) 1 For many patients, coordinated breathing can pose a challenge to therapy administration 2 Patients may unintentionally misuse or be nonadherent to COPD treatment, leading to less successful delivery of medication 2-5 According to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD): Incorrect inhalation technique, over time, is a major challenge to achieving COPD treatment goals 1 More than two-thirds of patients make at least 1 error using an inhalation device 1 The selection of inhalation device should depend on the patient s ability and preference 1 Note: NEOHALER is for use only with ARCAPTA, SEEBRI, and UTIBRON capsules. References: 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017:1-123. 2. Taffet GE, Donohue JF, Altman PR. Clin Interv Aging. 2014;9:23-30. 3. Fulvio B, et al. Int J Chron Obstruct Pulmon Dis. 2015;10:2601-2608. 4. Tashkin DP, et al. Respir Res. 2010;11(149):1-14. 5. Restrepo RD, et al. Int J Chron Obstruct Pulmon Dis. 2008;3(3):371-384. 3

Inhalation device options for COPD medication delivery Metered-dose inhaler 1-3 Soft-mist inhaler 3 Small and portable Coordination of breathing and actuation required (coordinated breath) No drug preparation; device shaking required Short administration time (seconds) Small and portable Requires specific breathing technique (coordinated breath) Multiple steps for setup and maintenance Short administration time (seconds) Dry-powder inhaler 3-6 Small and portable Breath-actuated Pill insertion required with certain devices Short administration time (seconds) Jet nebulizer 3,7 Can vary in size and portability Tidal breathing (several breaths over time) Multiple steps for setup and maintenance Administration time up to 20 minutes References: 1. Restrepo RD et al. Int J Chron Obstruct Pulmon Dis. 2008;3(3):371-384. 2. Tashkin DP. Int J Chron Obstruct Pulmon Dis. 2016;11:2585-2596. 3. Dolovich MB et al. Chest. 2005;127(1):335-371. 4. Lavorini F et al. Respir Med. 2008;102(4):593-604. 5. Al-Showair RA et al. Respir Med. 2007;101(11):2395-2401. 6. Virchow JC et al. Respir Med. 2008;102(1):10-19. 7. Dhand R et al. COPD. 2012;9(1):58-72. 4

The NEOHALER device: a delivery option for your COPD patient population

Consider attributes of the NEOHALER device1-4 Breath-actuated Audiovisual feedback mechanisms Small and portable For representation purposes only, UTIBRON NEOHALER is shown. ARCAPTA capsules, SEEBRI capsules, and UTIBRON capsules must not be swallowed as the intended effects on the lungs will not be obtained. ARCAPTA capsules, SEEBRI capsules, and UTIBRON capsules are only for oral inhalation and should only be used with the NEOHALER device. References: 1. Tashkin DP. Int J Chron Obstruct Pulmon Dis. 2016;11:2585-2596. 2. UTIBRON NEOHALER [prescribing information]. 3. SEEBRI NEOHALER [prescribing information]. 4. ARCAPTA NEOHALER [prescribing information]. 6

NEOHALER feedback mechanisms 1-3 The NEOHALER device allows patients to visualize whether there is any powder left in the capsule giving them the flexibility to inhale any remaining dose On inhalation, the capsule spins around in the chamber, producing a whirring noise. Patients are advised to open the NEOHALER device to ensure the capsule is empty. If any powder remains in the capsule, the patient should inhale the remaining powder. Most people are able to empty the capsule with 1 or 2 inhalations. IMPORTANT SAFETY INFORMATION All LABAs, including indacaterol, are contraindicated in patients with asthma without the use of a long-term asthma-control medication; ARCAPTA NEOHALER is also contraindicated in patients with a history of hypersensitivity to indacaterol or to any of the ingredients, and UTIBRON NEOHALER is contraindicated in patients with a history of hypersensitivity to indacaterol, glycopyrrolate, or to any of the ingredients. SEEBRI NEOHALER is contraindicated in patients with a hypersensitivity to glycopyrrolate or to any of the ingredients. References: 1. UTIBRON NEOHALER [prescribing information]. 2. SEEBRI NEOHALER [prescribing information]. 3. ARCAPTA NEOHALER [prescribing information]. 7

The 3 I's are an easy way for patients to remember the detailed instructions Always refer to the Instructions for Use for complete steps.1-3 Summary of the detailed steps: INSERT INHALE 1 UTIBRON or SEEBRI capsule twice daily for 24-hour bronchodilation 1 ARCAPTA capsule once daily for 24-hour bronchodilation Close the inhaler fully. You should hear a "click" as it fully closes Close the NEOHALER and press both piercing buttons together firmly to pierce the capsule, then fully release the buttons Distinct whirring sound during inhalation confirms the capsule is placed within the chamber correctly UTIBRON, SEEBRI, and ARCAPTA capsules are for oral inhalation only and should not be swallowed INSPECT Clear capsule design enables the patient to visualize whether there is any powder left in the capsule giving them the flexibility to inhale any remaining dose For representation purposes only, UTIBRON NEOHALER device and medication are shown. IMPORTANT SAFETY INFORMATION Immediate hypersensitivity reactions have been reported with ARCAPTA NEOHALER, SEEBRI NEOHALER, and UTIBRON NEOHALER. If signs occur, discontinue immediately and institute alternative therapy. ARCAPTA NEOHALER, SEEBRI NEOHALER, and UTIBRON NEOHALER should be used with caution in patients with severe hypersensitivity to milk proteins. References: 1. UTIBRON NEOHALER [prescribing information]. 2. SEEBRI NEOHALER [prescribing information]. 3. ARCAPTA NEOHALER [prescribing information]. 8

Summary Patient's ability to correctly take their COPD medication is important for selection of an appropriate device1 Choosing an appropriate inhalation device is important for COPD treatment goals1 The NEOHALER device was designed with patients needs in mind2-5 Breath actuated Provides audiovisual feedback mechanisms An easy way to remember the detailed instructions is to think of the 3 I's: Insert Inhale Inspect Small and portable IMPORTANT SAFETY INFORMATION ARCAPTA capsules, SEEBRI capsules, and UTIBRON capsules must not be swallowed as the intended effects on the lungs will not be obtained. ARCAPTA capsules, SEEBRI capsules, and UTIBRON capsules are only for oral inhalation and should only be used with the NEOHALER device. For representation purposes only, UTIBRON NEOHALER is shown. References: 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017:1-123. 2. Tashkin DP. Int J Chron Obstruct Pulmon Dis. 2016;11:2585-2596. 3. UTIBRON NEOHALER [prescribing information]. 4. SEEBRI NEOHALER [prescribing information]. 5. ARCAPTA NEOHALER [prescribing information]. 9

Important Safety Information INDICATION ARCAPTA NEOHALER (indacaterol) is a long-acting beta 2 -adrenergic agonist (LABA), SEEBRI NEOHALER (glycopyrrolate) is an anticholinergic, and UTIBRON NEOHALER (indacaterol and glycopyrrolate) is a combination of indacaterol and glycopyrrolate; all are indicated for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Important limitations: ARCAPTA NEOHALER and UTIBRON NEOHALER are not indicated to treat acute deteriorations of COPD and are not indicated to treat asthma. IMPORTANT SAFETY INFORMATION WARNING: ASTHMA-RELATED DEATH Long-acting beta 2 -adrenergic agonists (LABAs) increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of all LABAs, including indacaterol, the active ingredient in ARCAPTA NEOHALER, and one of the active ingredients in UTIBRON NEOHALER. The safety and efficacy of ARCAPTA NEOHALER or of UTIBRON NEOHALER in patients with asthma have not been established. ARCAPTA NEOHALER and UTIBRON NEOHALER are not indicated for the treatment of asthma. 10

Important Safety Information (cont d) All LABAs, including indacaterol, are contraindicated in patients with asthma without the use of a long-term asthma-control medication; ARCAPTA NEOHALER is also contraindicated in patients with a history of hypersensitivity to indacaterol or to any of the ingredients, and UTIBRON NEOHALER is contraindicated in patients with a history of hypersensitivity to indacaterol, glycopyrrolate, or to any of the ingredients. SEEBRI NEOHALER is contraindicated in patients with a hypersensitivity to glycopyrrolate or to any of the ingredients. ARCAPTA NEOHALER, SEEBRI NEOHALER, or UTIBRON NEOHALER should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD, or used as rescue therapy for acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled short-acting beta 2 -agonist. ARCAPTA NEOHALER or UTIBRON NEOHALER should not be used more often, at higher doses than recommended, or in conjunction with other medicines containing LABAs as an overdose may result. Patients who have been taking inhaled short-acting beta 2 -agonists on a regular basis should be instructed to discontinue their regular use and to use them only for symptomatic relief of acute respiratory symptoms. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using ARCAPTA NEOHALER or UTIBRON NEOHALER should not use another medicine containing a LABA for any reason. Immediate hypersensitivity reactions have been reported with ARCAPTA NEOHALER, SEEBRI NEOHALER, and UTIBRON NEOHALER. If signs occur, discontinue immediately and institute alternative therapy. ARCAPTA NEOHALER, SEEBRI NEOHALER, and UTIBRON NEOHALER should be used with caution in patients with severe hypersensitivity to milk proteins. As with other inhaled medicines, ARCAPTA NEOHALER, SEEBRI NEOHALER, and UTIBRON NEOHALER can produce paradoxical bronchospasm that may be life threatening. If paradoxical bronchospasm occurs following dosing with ARCAPTA NEOHALER, SEEBRI NEOHALER, or UTIBRON NEOHALER, it should be treated immediately with an inhaled, short-acting bronchodilator; ARCAPTA NEOHALER, SEEBRI NEOHALER, or UTIBRON NEOHALER should be discontinued immediately and alternative therapy instituted. 11

Important Safety Information (cont d) Indacaterol, like other beta 2 -adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. ARCAPTA NEOHALER or UTIBRON NEOHALER should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Beta 2 -adrenergic agonists may produce significant hypokalemia in some patients. As with other beta 2 -adrenergic agonists, indacaterol should be administered with extreme caution in patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval because these agents may potentiate the action of adrenergic agonists on the cardiovascular system. As with other beta 2 -adrenergic agonists, ARCAPTA NEOHALER and UTIBRON NEOHALER should be used with caution in patients treated with additional adrenergic drugs, non-potassium-sparing diuretics, and beta-blockers. ARCAPTA NEOHALER and UTIBRON NEOHALER, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines. SEEBRI NEOHALER or UTIBRON NEOHALER should be used with caution in patients with narrow-angle glaucoma and in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema) and of urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Patients should be instructed to consult a physician immediately should any signs or symptoms develop. 12

Important Safety Information (cont d) In 6 clinical trials, 48% of ARCAPTA NEOHALER patients reported adverse reactions compared with 43% of placebo patients. The most common adverse events reported in 2% of patients taking ARCAPTA NEOHALER, and occurring more frequently than in patients taking placebo, were cough (6.5% vs 4.5%), nasopharyngitis (5.3% vs 2.7%), headache (5.1% vs 2.5%), nausea (2.4% vs 0.9%), and oropharyngeal pain (2.2% vs 0.7%). The most common serious adverse reactions of ARCAPTA NEOHALER patients were COPD exacerbation, pneumonia, angina pectoris, and atrial fibrillation, which occurred at similar rates across treatment groups. The most common adverse events reported in 1% of patients taking SEEBRI NEOHALER, and occurring more frequently than in patients taking placebo, were upper respiratory tract infection (3.4% vs 2.3%), nasopharyngitis (2.1% vs 1.9%), oropharyngeal pain (1.8% vs 1.2%), urinary tract infection (1.4% vs 1.3%), and sinusitis (1.4% vs 0.7%). The most common adverse events reported in 1% of patients taking UTIBRON NEOHALER, and occurring more frequently than in patients taking placebo, were nasopharyngitis (4.1% vs 1.8%), hypertension (2.0% vs 1.4%), back pain (1.8% vs 0.6%), and oropharyngeal pain (1.6% vs 1.2%). ARCAPTA capsules, SEEBRI capsules, and UTIBRON capsules must not be swallowed as the intended effects on the lungs will not be obtained. ARCAPTA capsules, SEEBRI capsules, and UTIBRON capsules are only for oral inhalation and should only be used with the NEOHALER device. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. For additional information, please see accompanying full Prescribing Information, including BOXED WARNINGS and Medication Guides, for ARCAPTA NEOHALER and UTIBRON NEOHALER, and Patient Information for SEEBRI. 13

Thank you! UTIBRON,, SEEBRI, and are trademarks of Novartis AG, used under license. ARCAPTA,, and NEOHALER are registered trademarks of Novartis AG, used under license. SUNOVION and are registered trademarks of Sumitomo Dainippon Pharma Co., Ltd. Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Sumitomo Dainippon Pharma Co., Ltd. 14 9/17 RESP019-17